Potent ROS inhibitors from Zanthoxylum armatumDC of Nepali origin

Area of Science:

• Natural Product Chemistry
• Pharmacology
• Medicinal Chemistry

Background:

• Reactive oxygen species (ROS) are implicated in various inflammatory conditions.
• Phytochemical investigation of medicinal plants is a vital source for novel therapeutic agents.
• Zanthoxylum armatum is traditionally used for its medicinal properties.

Purpose of the Study:

• To isolate and characterize bioactive compounds from Zanthoxylum armatum.
• To evaluate the ROS inhibitory and antioxidant potential of isolated compounds.
• To investigate the anti-inflammatory mechanism via molecular docking and drug-likeness prediction.

Main Methods:

• Bioassay-guided fractionation of Zanthoxylum armatum ethyl acetate extract.
• Structure elucidation using mass spectrometry and Nuclear Magnetic Resonance (NMR) spectroscopy.
• In vitro antioxidant and ROS inhibition assays, molecular docking against COX-2, and ADMET prediction.

Main Results:

• Tambulin (1) and prudomestin (2) were isolated and identified.
• Both compounds demonstrated significant ROS inhibition (IC50 values: 7.5 ± 0.3 and 1.5 ± 0.3 µg/mL) and antioxidant activity (IC50 values: 32.65 ± 0.31 and 26.96 ± 0.19 µg/mL).
• Molecular docking revealed strong binding affinity to COX-2 (-8.4 to -8.6 kcal/mol), superior to ibuprofen (-7.7 kcal/mol), with favorable ADMET profiles.

Conclusions:

• Tambulin and prudomestin are potent ROS inhibitors and antioxidants with potential anti-inflammatory activity.
• The compounds exhibit favorable drug-like properties and good gastrointestinal absorption.
• Zanthoxylum armatum is a valuable source of novel anti-inflammatory agents.